dc.contributor.author |
Walsh, Jacinta |
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dc.contributor.author |
Gheorghe, Cassandra E. |
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dc.contributor.author |
Lyte, Joshua M. |
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dc.contributor.author |
van de Wouw, Marcel |
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dc.contributor.author |
Boehme, Marcus |
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dc.contributor.author |
Dinan, Timothy G. |
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dc.contributor.author |
Cryan, John F. |
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dc.contributor.author |
Griffin, Brendan T. |
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dc.contributor.author |
Clarke, Gerard |
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dc.contributor.author |
Hyland, Niall P. |
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dc.date.accessioned |
2020-04-28T14:21:48Z |
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dc.date.available |
2020-04-28T14:21:48Z |
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dc.date.issued |
2020-04-26 |
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dc.identifier.citation |
Walsh, J., Gheorghe, C.E., Lyte, J.M., van de Wouw, M., Boehme, M., Dinan, T.G., Cryan, J.F., Griffin, B.T., Clarke, G. and Hyland, N.P. (2020) 'Gut microbiome‐mediated modulation of hepatic cytochrome P450 and P‐glycoprotein: impact of butyrate and fructo‐oligosaccharide‐inulin', Journal of Pharmacy and Pharmacology, doi: 10.1111/jphp.13276 |
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dc.identifier.startpage |
1 |
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dc.identifier.endpage |
10 |
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dc.identifier.issn |
2042-7158 |
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dc.identifier.uri |
http://hdl.handle.net/10468/9885 |
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dc.identifier.doi |
10.1111/jphp.13276 |
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dc.description.abstract |
Objectives: Our objective was to demonstrate microbial regulation of hepatic genes implicated in drug metabolism and transport using germ‐free (GF) mice and to explore the impact of a microbial metabolite, butyrate, and a prebiotic dietary intervention on hepatic gene expression in mice. Methods: Using reverse‐transcriptase PCR, we investigated cytochrome P450 (CYP) and multidrug‐resistance protein 1 (MDR1) expression in conventional, GF and colonised GF mice. To investigate the effects of butyrate, sodium butyrate (3 g/l) was administered for 21 days to conventional or GF mice. In the prebiotic study, young adult and middle‐aged mice received diet enriched with 10% fructo‐oligosaccharide (FOS)‐inulin for 14 weeks. Key findings: Colonisation of GF animals normalised expression of Cyp3a11 and Mdr1b to conventional levels. Butyrate upregulated Cyp2b10 in conventional mice (P < 0.05) but overall did not induce widespread changes in hepatic genes. FOS‐inulin increased Cyp3a13 expression and had the opposite effect on Mdr1a expression in young adult mice (P < 0.05). Age, on the other hand, influenced the prebiotic effect on Cyp2a4 expression (P < 0.01). Conclusion: The expression of hepatic genes implicated in drug metabolism and transport displays sensitivity to the microbiome, microbiome‐derived metabolites and a microbial‐targeted intervention. Our study may provide the impetus to explore microbiota‐targeted interventions in normalising host metabolic activity and reducing inter‐individual variability in drug pharmacokinetics. |
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dc.description.sponsorship |
Nature Research-Yakult (The Global Grants for Gut Health; Ref No. 626891); Joint Programming Initiative-a healthy diet for a healthy life ((JPI-HDHL) award, ‘A Menu for Brain Responses Opposing Stress-Induced Alternations in Cognition’ (AMBROSIAC; 15/JPHDHL/3270)) |
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dc.format.mimetype |
application/pdf |
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dc.language.iso |
en |
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dc.publisher |
Wiley |
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dc.rights |
© 2020 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology. This is the peer reviewed version of the following article: (2020), Gut microbiome‐mediated modulation of hepatic cytochrome P450 and P‐glycoprotein: impact of butyrate and fructo‐oligosaccharide‐inulin. J Pharm Pharmacol., which has been published in final form at https://doi.org/10.1111/jphp.13276 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
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dc.subject |
Cytochrome |
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dc.subject |
Hepatic |
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dc.subject |
Metabolism |
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dc.subject |
Microbiome |
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dc.subject |
Transporter |
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dc.title |
Gut microbiome-mediated modulation of hepatic cytochrome P450 and P-glycoprotein: impact of butyrate and fructo-oligosaccharide-inulin |
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dc.type |
Article (peer-reviewed) |
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dc.internal.authorcontactother |
Niall Hyland, Physiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: n.hyland@ucc.ie |
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dc.internal.availability |
Full text available |
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dc.check.info |
Access to this article is restricted until 12 months after publication by request of the publisher. |
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dc.check.date |
2021-04-26 |
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dc.date.updated |
2020-04-28T13:08:48Z |
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dc.description.version |
Accepted Version |
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dc.internal.rssid |
512189042 |
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dc.internal.pmid |
32337713 |
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dc.contributor.funder |
Science Foundation Ireland
|
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dc.contributor.funder |
Yakult Bio-Science Foundation
|
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dc.contributor.funder |
Joint Programming Initiative A healthy diet for a healthy life
|
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dc.description.status |
Peer reviewed |
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dc.identifier.journaltitle |
Journal of Pharmacy and Pharmacology |
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dc.internal.copyrightchecked |
Yes |
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dc.internal.licenseacceptance |
Yes |
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dc.internal.IRISemailaddress |
n.hyland@ucc.ie |
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dc.internal.IRISemailaddress |
jacinta.walsh@ucc.ie |
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dc.internal.IRISemailaddress |
brendan.griffin@ucc.ie |
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dc.internal.IRISemailaddress |
marcus.boehme@ucc.ie |
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dc.internal.IRISemailaddress |
j.cryan@ucc.ie |
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dc.internal.IRISemailaddress |
t.dinan@ucc.ie |
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dc.internal.IRISemailaddress |
g.clarke@ucc.ie |
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dc.internal.bibliocheck |
In press. Add volume, pages, update citation. |
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dc.relation.project |
info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/
|
en |